Recruiting
Phase 1

AMG 410

Sponsor:

Amgen

Code:

NCT07094113

Conditions

KRAS Altered Advanced or Metastatic Solid Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

AMG 410

Pembrolizumab

Panitumumab

Study Details

Brief summary:

The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AMG 410 when administered alone or in combination with other agents in participants with advanced or metastatic solid tumors harboring KRAS alterations.

This is a dose-escalation study in which participants will be assigned to multiple dose levels (DLs) of AMG 410, either as monotherapy or in combination with other agents, followed by expansion cohorts. The goal is to determine the Maximum Tolerated Dose (MTD)-the highest dose with acceptable safety and manageable side effects-or the Recommended Phase 2 Dose (RP2D) of AMG 410 in adult participants with KRAS-altered advanced or metastatic solid tumors.

Conditions

KRAS Altered Advanced or Metastatic Solid Tumors

Study ID

NCT07094113

Start date

Jul 31, 2025

Status verified date

Jul, 2026

Completion date

Apr 20, 2031

Anticipated

Primary completion date

Apr 18, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Age ≥ 18 years (or > legal age within the country if it is older than 18 years).
2. Pathologically documented, locally-advanced or metastatic malignancy with any missense mutation in the KRAS gene or evidence of KRAS amplification using an analytically validated KRASWT amplification assay.
3. Participants must have no standard of care treatment options or have actively refused such therapy.
4. Able to swallow and retain per oral administered study treatment.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
6. Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as determined by the site investigator.
7. Adequate organ function.
8. Archival (formalin-fixed, paraffin-embedded \[FFPE\]) tumor tissue or block collected within 5 years before screening must be available. Participants without archived tumor tissue may undergo tumor biopsy before AMG 410 dosing (Day1).

Exclusion Criteria:

1. Untreated symptomatic central nervous system or leptomeningeal metastases.
2. Uncontrolled pleural effusion and/or ascites.
3. History of other malignancy within the past 5 years.
4. Active systemic infection or symptoms that indicate an acute and/or uncontrolled infection requiring IV antibiotics within 7days prior to the first dose of study treatment.
5. History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis).
6. Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of study treatment.
7. History of solid organ transplant.
8. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 28 days of first dose of study treatment.
9. Presence or history of any of the following viral infections: HIV, Hepatitis C, Hepatitis B, and active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
10. Toxicities from prior anti-tumor therapy (including radiotherapy) not having improved to at least Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1.
11. Therapeutic or palliative radiation therapy within 2 weeks of first dose of study treatment.
12. Major surgery within 28 days of first dose of study treatment.
13. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.

Study Design

Enrollment

434 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1: Monotherapy Dose Exploration

Participants will receive escalating doses of AMG 410.

experimental: Part 1: Food Effect Substudy Cohort

A food effect substudy will be conducted. During the substudy, participants will receive AMG 410 under fasted and fed conditions.

experimental: Part 1: China-specific Cohort

Participants identified through regionally approved molecular KRAS testing will receive AMG 410.

experimental: Part 2: Monotherapy Dose Expansion

Monotherapy dose expansion of AMG 410 may proceed in KRAS altered tumors in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and other KRAS altered tumor types.

experimental: Part 3a: Combination Therapy Dose Exploration and Dose Expansion

Part 3a allows for AMG 410 dose exploration and expansion in combination with pembrolizumab in KRAS altered advanced or metastatic solid tumors.

experimental: Part 3b: Combination Therapy Dose Exploration and Dose Expansion

Part 3b allows for AMG 410 dose exploration and expansion in combination with panitumumab in advanced or metastatic CRC and/or PDAC.

Interventions

AMG 410

Administered as an oral tablet.

Pembrolizumab

Administered as an intravenous (IV) infusion.

Panitumumab

Administered as an IV infusion.

Primary outcome measure

  • Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
  • Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 3 years ]
  • Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 3 years ]

Central Contacts and Locations

Central contacts

Locations

City of Hope National Medical Center

Recruiting

Duarte, California, United States, 91010

University of California Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Siteman Cancer Center - Washington University

Recruiting

St Louis, Missouri, United States, 63110

Duke Cancer Center

Recruiting

Durham, North Carolina, United States, 27710

Thomas Jefferson University

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Sarah Cannon Research Institute Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Next Oncology

Recruiting

San Antonio, Texas, United States, 78229

Next Virginia

Recruiting

Fairfax, Virginia, United States, 22031

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 1Z5

Sir Mortimer B Davis - Jewish General Hospital

Recruiting

Montreal, Quebec, Canada, H3T 1E2

More Information

Sponsor

Amgen

Last update posted

Jul 30, 2026

Last verified

Jul, 2026

Keywords

  • Non-small cell lung cancer
  • NSCLC
  • Colorectal cancer
  • CRC
  • Pancreatic ductal adenocarcinoma
  • PDAC
  • AMG 410

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Amgen on 2026-07-30.